STAT6 signaling pathway controls germinal center responses promoted after antigen targeting to conventional type 2 dendritic cells.

Autor: Sulczewski FB; Departamento de Parasitologia, Instituto de Ciencias Biomedicas, Universidade de Sao Paulo, Sao Paulo, Brazil., Martino LA; Departamento de Parasitologia, Instituto de Ciencias Biomedicas, Universidade de Sao Paulo, Sao Paulo, Brazil., da Silva Almeida B; Departamento de Parasitologia, Instituto de Ciencias Biomedicas, Universidade de Sao Paulo, Sao Paulo, Brazil., Yamamoto MM; Departamento de Parasitologia, Instituto de Ciencias Biomedicas, Universidade de Sao Paulo, Sao Paulo, Brazil., Rosa DS; Departamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de Sao Paulo, Sao Paulo, Brazil.; Instituto de Investigação em Imunologia (iii), INCT, Sao Paulo, Brazil., Boscardin SB; Departamento de Parasitologia, Instituto de Ciencias Biomedicas, Universidade de Sao Paulo, Sao Paulo, Brazil.; Instituto de Investigação em Imunologia (iii), INCT, Sao Paulo, Brazil.
Jazyk: angličtina
Zdroj: Current research in immunology [Curr Res Immunol] 2021 Aug 28; Vol. 2, pp. 120-131. Date of Electronic Publication: 2021 Aug 28 (Print Publication: 2021).
DOI: 10.1016/j.crimmu.2021.08.001
Abstrakt: Conventional dendritic cells (cDCs) are antigen-presenting cells specialized in naïve T cell priming. Mice splenic cDCs are classified as cDC1s and cDC2s, and their main functions have been elucidated in the last decade. While cDC1s are specialized in priming type 1 helper T cells (T H 1) and in cross presentation, cDC2s prime T follicular helper (T FH ) cells that stimulate germinal center (GC) formation, plasma cell differentiation and antibody production. However, less is known about the molecular mechanisms used by cDCs to prime those responses. Here, using WT and STAT6-deficient mice (STAT6 KO), we targeted a model antigen to cDC1s and cDC2s via DEC205 and DCIR2 receptors, respectively, in an attempt to study whether the STAT6 signaling pathway would modulate cDCs' ability to prime helper T cells. We show that the differentiation and maturation of cDCs, after stimulation with an adjuvant, were comparable between WT and STAT6 KO mice. Besides, our results indicate that, in STAT6 KO mice, antigen targeting to cDC2s induced reduced T FH and GC responses, but did not alter plasma cells numbers and antibody titers. Thus, we conclude that the STAT6 signaling pathway modulates the immune response after antigen targeting to cDC2s via the DCIR2 receptor: while STAT6 stimulates the development of T FH cells and GC formation, plasma cell differentiation occurs in a STAT6 independent manner.
Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(© 2021 The Authors.)
Databáze: MEDLINE
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